Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast.
Autophagy is a bulk protein degradation process that is induced by starvation. The control mechanism for induction of autophagy is not well understood. We found that Tor, a phosphatidylinositol kinase homologue, is involved in the control of autophagy in the yeast, Saccharomyces cerevisiae. When rapamycin, an inhibitor of Tor function, is added, autophagy is induced even in cells growing in nutrient-rich medium. A temperature-sensitive tor mutant also leads to induction of autophagy at a nonpermissive temperature. These results indicate that Tor negatively regulates the induction of autophagy. Tor is the first molecule that is identified as a pivotal player in the starvation-signaling pathway of autophagy. Furthermore, we found that a high concentration of cAMP is inhibitory for induction of autophagy. APG gene products are involved in autophagy induced by starvation. Autophagy was not induced in apg mutants in the presence of rapamycin, indicating that the site of action of Tor is upstream of those of Apg proteins. In nutrient-rich medium, Apg proteins are involved also in the transport of aminopeptidase I from the cytosol to the vacuole. Tor may act to switch Apg function between autophagy and transport of aminopeptidase I.
Noda
T
T
National Institute for Basic Biology, Department of Cell Biology, Nishigonaka 38, Myodaijicho, Okazaki 444, Japan.
Ohsumi
Y
Y
D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000626:Aminopeptidases / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011090:Polyenes / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus